Field of the Invention
The present invention relates to the field of Ion Mobility Mass Spectroscopy (IMMS). More particularly, the present invention relates to a Perturbation Ion Mobility Mass Spectrometry (PIMMS) methodology and system to enhance, for example, ion efficiency and thus sensitivity using such instrumentation.
Discussion of the Related Art
The utility of ion mobility spectrometry (IMS) for separation of ions has been demonstrated extensively, but IMS combined with mass spectrometry (MS) has remained a niche technique, mainly because of the loss of sensitivity due to ion losses within the combination of techniques. IMS, in particular, remains a needed and desired technique to be coupled with MS because of the speed of the separation technique. Specifically, IMS exploits the beneficial aspect that different particles diffuse through a gas at different speeds, depending on their collision cross-sections with the introduced gas molecules. While neutrals diffuse randomly (via Brownian motion), ions in an applied electric field drift in a defined direction with the velocity controlled by their mobility (K). Such a quantity generally varies with the field intensity E but IMS is often run in a low-field regime where K (E) is substantially constant. In that limit, K depends on the ion/buffer gas collision cross-section 106 , which allows a spatial separation of different ions.
The IMS concept of measuring size-to-charge ratio is also beneficially complementary to the principle of measurement in mass spectrometry (MS) of mass-to-charge ratio (m/z). When combined with MS, ion mobility-mass spectrometry (IMMS) represents a powerful analytical combination capable of distinguishing ions based upon both size and mass-to-charge ratios. A particular beneficial IMS analytical tool is a drift-tube ion mobility spectrometer (DT-IMS) based on the ability to rapidly screen passengers, cargo, and the surrounding environment for narcotics, explosives, and chemical warfare agents. DT-IMS also finds utility as an informative tool to probe gas-phase ion chemistry, kinetics, and under select conditions gas-phase ion conformations. DT-IMS refers to all ion mobility separation devices that cause ions to arrive at a detector at different times based on their ion mobilities; these devices sometimes are called by different names or abbreviations, e.g. traveling wave ion mobility separation device. As with many time-dispersive techniques however, challenges related to duty cycle are quite common when utilizing DT-IMS instruments. The duty cycle in most DT-IMS experiments is usually on the order of <1% and this limitation in ion throughput naturally impacts sensitivity. Despite this limitation, a suite of vendors have begun producing a range of mobility-based instruments, including DT-IMS systems, for the research community, and this access has further propelled adoption of the technique. While these ion mobility-mass spectrometry (IMMS) instruments enable for a broad class of researcher, they are still limited by duty cycle and sensitivity, which constrains their ultimate potential. These classic trade-offs are by no means new problems, but few solutions have been wholly adopted by the community.
Particular solutions applied to combat the duty cycle problem include multiplexing approaches such as Fourier and Hadamard pulsing schemes, which independently enhance the throughput of ion mobility spectrometry (IMS) experiments. Historically however, FT-IMS experiments, for example, never realized the full Signal to Noise Ratio (SNR) potential suggested by theory. As a result, challenges nonetheless remain as to the broad scale implementation using such techniques when utilized with ion mobility mass spectrometry (IMMS) instruments.
Accordingly, a need exists for a hybrid Perturbation Ion Mobility Mass Spectrometry (PIMMS) system and methodology that increases the system's duty cycle and sensitivity while maintaining equivalent resolving power. In the embodiments herein, ions are continuously introduced into a drift tube cell of a configured ion mobility spectrometer and then periodically, the continuous ion beam is perturbed and the perturbation continues to travel through the tube with the mobility matching the ions in the ion beam. By monitoring the disappearance of an ion in the mass spectrometer, the ion mobility spectrum is reconstructed and the size of an ion (its mobility) is measured as a function of its mass. In addition to an improvement in duty cycle, perturbation IMMS can additionally be used with MSMS techniques and is particularly useful for coupling to chromatographic separation instrumentation and methodologies.